Apparatus, systems, and methods for localizing markers or tissue structures within a body

ABSTRACT

Apparatus, systems, and methods are provided for localizing lesions within a patient&#39;s body, e.g., within a breast. The system may include one or more markers implantable within or around the target tissue region, and a probe for transmitting and receiving electromagnetic signals to detect the one or more markers. During use, the marker(s) are into a target tissue region, and the probe is placed against the patient&#39;s skin to detect and localize the marker(s). A tissue specimen, including the lesion and the marker(s), is then removed from the target tissue region based at least in part on the localization information from the probe.

RELATED APPLICATION DATA

This application claims benefit of co-pending provisional applicationsSer. Nos. 61/220,900, filed Jun. 26, 2009, 61/255,469, filed Oct. 27,2009, and 61/297,694, filed Jan. 22, 2010, the entire disclosures ofwhich are expressly incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates generally to apparatus and methods forperforming surgical procedures, and more particularly to apparatus andmethods for localizing targets, markers, lesions, and/or other bodystructures within a patient's body, e.g., during surgical or otherprocedures, such as during lumpectomy procedures.

BACKGROUND

Before a biopsy or surgical procedure to remove a lesion within abreast, such as a lumpectomy procedure, the location of the lesion mustbe identified. For example, mammography or ultrasound imaging may beused to identify and/or confirm the location of the lesion before aprocedure. The resulting images may be used by a surgeon during aprocedure to identify the location of the lesion and guide the surgeon,e.g., during dissection to access and/or remove the lesion. However,such images are generally two dimensional and therefore provide onlylimited guidance for localization of the lesion since the breast and anylesion to be removed are three-dimensional structures. Further, suchimages may provide only limited guidance in determining a proper marginaround the lesion, i.e., defining a desired specimen volume to beremoved.

To facilitate localization, immediately before a procedure, a wire maybe inserted into the breast, e.g., via a needle, such that a tip of thewire is positioned at the location of the lesion. Once the wire ispositioned, it may be secured in place, e.g., using a bandage or tapeapplied to the patient's skin where the wire emerges from the breast.With the wire placed and secured in position, the patient may proceed tosurgery, e.g., to have a biopsy or lumpectomy performed.

One problem with using a wire for localization is that the wire may movebetween the time of placement and the surgical procedure. For example,if the wire is not secured sufficiently, the wire may move relative tothe tract used to access the lesion and consequently the tip maymisrepresent the location of the lesion. If this occurs, when thelocation is accessed and tissue removed, the lesion may not be fullyremoved and/or healthy tissue may be unnecessarily removed. In addition,during the procedure, a surgeon merely estimates the location of thewire tip and lesion, e.g., based on mammograms or other images obtainedduring wire placement, and may proceed with dissection without anyfurther guidance. Again, since such images are two dimensional, they mayprovide limited guidance to localize the lesion being treated orremoved.

Alternatively, it has been suggested to place a radioactive seed toprovide localization during a procedure. For example, a needle may beintroduced through a breast into a lesion, and then a seed may bedeployed from the needle. The needle may be withdrawn, and the positionof the seed may be confirmed using mammography. During a subsequentsurgical procedure, a hand-held gamma probe may be placed over thebreast to identify a location overlying the seed. An incision may bemade and the probe may be used to guide excision of the seed and lesion.

Because the seed is delivered through a needle that is immediatelyremoved, there is risk that the seed may migrate within the patient'sbody between the time of placement and the surgical procedure. Thus,similar to using a localization wire, the seed may not accuratelyidentify the location of the lesion, particularly, since there is noexternal way to stabilize the seed once placed. Further, such gammaprobes may not provide desired precision in identifying the location ofthe seed, e.g., in three dimensions, and therefore may only providelimited guidance in localizing a lesion.

Accordingly, apparatus and methods for localization of lesions or othertissue structures in advance of and/or during surgical, diagnostic, orother medical procedures would be useful.

SUMMARY OF THE INVENTION

The present invention is directed to apparatus and methods forperforming surgical or other medical procedures. More particularly, thepresent invention is directed to implantable markers and to apparatusand methods for localizing targets, markers, lesions, and/or othertissue structures within a patient's body during surgical or othermedical procedures, e.g., for localizing breast lesions before or duringlumpectomy procedures.

In accordance with one embodiment, a system is provided for localizationof a target tissue region within a patient's body that includes one ormore markers or targets; and a probe for transmitting and receivingelectromagnetic signals to detect a target after the target isintroduced into a target tissue region and the probe is placed adjacentand/or aimed towards the target tissue region. The probe may include oneor more output devices, e.g., a display, speaker, and the like, thatprovide spatial information based on the spatial relationship of thetarget relative to the probe, e.g., a distance and/or angularorientation between the probe and the target. Optionally, the system mayalso include one or more delivery devices for introducing the target(s)into tissue or otherwise into a patient's body, e.g., including aneedle, cannula, or other tubular member within which one or moretargets may be loaded.

In an exemplary embodiment, the target may include a plurality of angledsurfaces that may enhance reflection of the electromagnetic signals fromthe probe, e.g., such that the target provides a passive marker. Forexample, the target may be an elongate marker including a plurality ofbeads coupled to a core element, the beads including angled surfacesand/or edges to enhance detection by the probe. The core element may bebiased to one or more predetermined shapes, e.g., a wave shape, atapered helix, a cylindrical helix, and the like, yet may besufficiently resilient to be straightened, e.g., to facilitate loadingthe marker into a delivery device. In another embodiment, the target mayinclude a spherical, elliptical, discus, or other shape, e.g., includingone or more surface features to enhance reflection of theelectromagnetic signals.

Optionally, the target may include one or more circuits, features, andthe like that modulate an incident signal from the probe to facilitateidentification of the target, e.g., such that the target provides anactive reflector marker. For example, the target may impose a phaseshift on signals from the probe that strike the target, e.g., todistinguish the target from other targets, tissue structures, and thelike. In another option, the target may include a circuit and powersource such that the target may generate predetermined signals inresponse to detecting a signal from the probe, e.g., to provide anactive transponder marker.

Optionally, the target may include a marker releasably or substantiallypermanently coupled to an elongate flexible tether. Alternatively, thetarget may include a localization wire including a shaft and a marker ona distal end of the shaft.

In accordance with another embodiment, a system is provided forlocalization of a target tissue region within a patient's body thatincludes a delivery device carrying one or more markers or targets sizedfor implantation within or around the target tissue region; and a probefor transmitting and receiving electromagnetic signals to detect the oneor more markers implanted within or around the target tissue region whenthe probe is placed adjacent the target tissue region and/or aimed atthe target tissue region.

In an exemplary embodiment, the delivery device may include a shaftincluding a proximal end and a distal end sized for introduction throughtissue within a patient's body into a target tissue region, and one ormore markers deliverable from the distal end. For example, the shaft mayinclude a lumen and a plurality of markers may be carried within thelumen such that the markers may be delivered sequentially from the shaftand implanted in locations within or around a lesion or other targettissue region. Exemplary markers that may be delivered with the deliverydevice may include a passive marker, an active reflector marker, and anactive transponder marker.

In accordance with still another embodiment, a method is provided forlocalizing a target tissue region within a patient's body that includesintroducing a marker or other target through tissue into the targettissue region; placing a probe against the patient's skin or otherwiseadjacent the target tissue region and/or aimed towards the target tissueregion; and activating the probe, whereupon the probe transmitselectromagnetic signals towards the target tissue region, receiveselectromagnetic signals reflected from the target, and displays, emits,or otherwise provides spatial information to provide a spatialrelationship between the target and the probe.

In one embodiment, the target may be a localization wire introducedthrough the tissue into the target tissue region, the localization wirecarrying the target. In another embodiment, the target may be one ormore markers implanted within the target tissue region. In yet anotherembodiment, the target may be a catheter or other device, e.g., that maybe introduced into a target region and deployed to delineate a volume orregion. The device may include special features that are configured forlocating and/or defining the volume, e.g., using an electromagnetic waveprobe. Optionally, the target may be placed before or during adiagnostic, therapeutic, and/or surgical procedure, e.g., usingstereotactic, ultrasound, or electromagnetic wave based imaging.

In an exemplary embodiment, the target tissue region may include aregion within a patient's breast having a lesion therein, and the targetmay be delivered into or around the lesion. Alternatively, the targettissue region may be located in other regions of the body, e.g., withinor around the intestines, fallopian tubes, and the like. For example,the target may include a first marker that is introduced into the targettissue region spaced apart from a lesion to define a desired margin forremoval of a specimen volume from the target tissue region. Optionally,a second marker and/or a plurality of additional markers may beintroduced into the target tissue region spaced apart from the lesionand the first marker to further define the desired margin. Thus, ifdesired, a three dimensional array of markers may be placed within oraround the target tissue region to facilitate localization thereof. Atissue specimen may then be removed from the target tissue region, thetissue specimen including the lesion and the target.

In accordance with yet another embodiment, a method is provided forremoving a lesion within a target tissue region of a patient's breastthat includes introducing a target through breast tissue into the targettissue region; placing a probe adjacent the patient's skin, e.g.,oriented generally towards the target tissue region, the probetransmitting electromagnetic signals towards the target tissue region,receiving electromagnetic signals reflected from the target, andproviding spatial information to provide a spatial relationship betweenthe target and the probe; and removing a tissue specimen from the targettissue region, the tissue specimen including the lesion and the target.

In accordance with still another embodiment, a method is provided forremoving a lesion within a target tissue region of a patient's breastthat includes introducing a target through breast tissue into the targettissue region; placing a probe adjacent the patient's skin, e.g.,oriented generally towards the target tissue region, the probetransmitting electromagnetic signals towards the target tissue regionand receiving electromagnetic signals reflected from the target; usingthe probe to determine a desired margin within the target tissue regionaround the lesion; and removing a tissue specimen from the target tissueregion, the tissue specimen defined by the desired margin and includingthe lesion and the target.

In accordance with yet another embodiment, an implantable marker isprovided for localization of a target tissue region within a patient'sbody that includes an elongate core member, and a plurality of beadscarried by the core member. Optionally, the beads may include aplurality of surfaces and/or edges to enhance reflection ofelectromagnetic signals to facilitate identification of the marker. Inaddition or alternatively, the marker may include an electronic circuit,e.g., embedded in or otherwise carried by one of the beads or the coremember, that may provide one of an active reflector and an activetransponder.

Other aspects and features of the present invention will become apparentfrom consideration of the following description taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view of an exemplary embodiment of a system forlocalizing a target tissue region within a body including a localizationwire and a probe.

FIG. 2A is a front elevation view of a torso of a patient's body,showing the localization wire of FIG. 1 being inserted into a targettissue region within a breast, e.g., a tumor or other lesion.

FIG. 2B is a cross-sectional view of the breast, taken along line 2B-2Bin FIG. 2A, showing a target on the localization wire disposed withinthe target tissue region.

FIG. 3 is a cross-sectional view of the breast depicted in FIGS. 2A and2B, showing the probe of FIG. 1 being used to take a first distancemeasurement to the target of the localization wire, e.g., to determinethe distance from the skin to the lesion, a desired margin, and/or asize of a specimen to be removed from the breast.

FIG. 4 is a cross-sectional view of the breast depicted in FIGS. 2A, 2B,and 3 after initial dissection has been performed, showing the probebeing used to take a second distance measurement, e.g., to determinewhether the tissue has been dissected sufficiently to reach the desiredmargin for the specimen to be removed.

FIG. 5 is cross-sectional view of an excised tissue specimen taken fromthe breast of FIGS. 2A and 2B, showing the probe being used to take athird distance measurement, e.g., to confirm that the desired marginaround the lesion has been achieved.

FIG. 6 is a perspective view of a breast, showing a delivery devicebeing used to deliver a plurality of markers around one or more lesions,e.g., a group of non-palpable lesions, within the breast.

FIG. 7 is a cross-sectional view of the breast of FIG. 6, showing aplurality of markers placed around the lesions.

FIG. 8 is a cross-sectional view of the breast depicted in FIGS. 6 and7, showing a probe being used to take a first set of distancemeasurements, e.g., to determine a distance to one or more of themarkers.

FIG. 9 is a cross-sectional view of the breast depicted in FIGS. 6-8,showing the probe being used to facilitate dissection down to themarkers, e.g., to define a desired margin around a specimen to beremoved from the breast.

FIG. 10 is a schematic showing an exemplary embodiment of a probe thatmay be included in various systems for localizing markers.

FIG. 10A is an exemplary display output that may be provided on a probe,such as the probe instrument shown in FIG. 10.

FIG. 10B is a cross-sectional view of an antenna that may be provided ina probe, such as that shown in FIG. 10.

FIG. 11 shows another exemplary embodiment of a system for localizing atarget tissue region within a body including a marker implanted in abreast and a probe instrument including a handheld probe for locatingthe marker and a controller coupled to the probe.

FIGS. 12-15 are side views of the system of FIG. 11 being used to locatethe marker to facilitate removing a tissue specimen from the breastincluding the lesion.

FIG. 14A is a detail from FIG. 14, showing the probe being used tolocate the marker and thereby identify a desired margin for the tissuespecimen being removed the breast.

FIG. 15A is a detail from FIG. 15, showing the probe being used tolocate the marker and thereby confirm that the desired margin for theremoved tissue specimen has been achieved.

FIG. 16A is a perspective view of another exemplary embodiment of aprobe instrument including a finger cot with integral probe and acontroller coupled to the probe.

FIG. 16B is a side view detail of the finger cot of FIG. 16A showing afinger received therein.

FIGS. 17 and 18 are cross-sectional views of a breast showing a markerimplanted adjacent lesions and located using the probe instrument ofFIGS. 16A and 16B during dissection of breast tissue to remove a tissuespecimen including the lesions.

FIG. 19 is a side view of yet another exemplary embodiment of a probeinstrument including a cannula carrying a probe and a controller coupledto the probe.

FIG. 19A is a detail of a sharpened distal tip of the cannula of FIG. 19showing the probe therein.

FIGS. 20-22 are cross-sectional views of a breast having a markerimplanted adjacent lesions and showing a method for placing the cannulainto the breast to provide access to the site of the lesions.

FIG. 23A is a side view of a first exemplary embodiment of an elongatemarker that may be implanted into tissue and located using a probe.

FIG. 23B is a cross-sectional view of the marker of FIG. 23A taken alongline 23B-23B.

FIG. 23C is an end view of the marker of FIG. 23A.

FIG. 23D is a side view of the marker of FIGS. 23A-23C having a waveshape in its deployed configuration.

FIGS. 24A-24C are perspective, end, and side views, respectively, of abead that may be used for making an implantable marker, such as themarker of FIGS. 23A-23D.

FIG. 25A is a side view of an alternative embodiment of an elongatemarker that may be implanted into tissue and located using a probe.

FIG. 25B is a detail of the marker of FIG. 24A showing featuresincorporated into the surface finish of the marker.

FIGS. 26A-26C are side, perspective, and end views, respectively, ofanother alternative embodiment of an elongate marker having a helicalconfiguration that may be implanted into tissue and located using aprobe.

FIGS. 27A-27C are perspective, end, and side views, respectively, of anexemplary embodiment of a spherical marker that may be implanted intotissue and located using a probe.

FIGS. 28A-28C are perspective views of alternative embodiments of aspherical marker that may be implanted into tissue and located using aprobe.

FIGS. 29A and 29B are side views of an exemplary embodiment of adelivery cannula being used to deliver the marker of FIG. 25 into abreast.

FIG. 30A is a side view of another exemplary embodiment of a deliverycannula for delivering a marker.

FIG. 30B is a cross-sectional view of the delivery cannula of FIG. 30Ataken along line 30B-30B.

FIG. 31A is a side view of the delivery cannula of FIGS. 30A and 30Bafter delivering the marker.

FIG. 31B is a cross-sectional view of the delivery cannula of FIG. 31Ataken along line 31B-31B.

FIGS. 32 and 33 are cross-sectional views of a breast showing a methodfor implanting the marker of FIG. 25 into the breast using the deliverycannula of FIGS. 30A-31B.

FIGS. 33A and 33A are details of the marker being implanted in thebreast as shown in FIGS. 32 and 33, respectively.

FIGS. 34A and 34B are side and end views, respectively, of yet anotherexemplary embodiment of a marker for implantation in tissue.

FIG. 35 is a side view of an alternative embodiment of a marker deviceincluding the marker of FIGS. 34A and 34B coupled to an elongate tether.

FIGS. 36-40 are cross-sectional views of a breast showing a deliverydevice for delivering the marker of FIG. 35 and showing a method forintroducing the deliver device into the breast to implant the markeradjacent one or more lesions.

FIGS. 41A and 41B are side and end views, respectively, of still anotherexemplary embodiment of a marker for implantation in tissue.

FIG. 42 is a side view of an alternative embodiment of a marker deviceincluding the marker of FIGS. 36A and 36B coupled to an elongate tether.

FIGS. 43-46 are cross-sectional views of a breast showing a deliverydevice for delivering the marker of FIG. 42 and showing a method forintroducing the deliver device into the breast to implant the markeradjacent one or more lesions.

FIG. 47 is a cross-sectional view of a patient's body showing markersbeing introduced into the patient's gastrointestinal system.

FIG. 48 is a detail of a marker that may be introduced into thepatient's body shown in FIG. 47.

FIG. 49 is a detail of the patient's body of FIG. 47, showinginstruments being introduced into the patient's body based at least inpart on the location of a marker introduced into the patient'sgastrointestinal system in order to perform a procedure.

FIG. 50A is a schematic representation of a signal from a probe strikingand reflecting from a marker, while FIG. 50B shows a phase shift betweenthe incident signal and the reflected signal.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

Turning to the drawings, FIG. 1 shows an exemplary embodiment of asystem 10 for localization of a target tissue region within a patient'sbody, such as a tumor, lesion, or other tissue structure within a breastor other location within a body. The system 10 generally includes amarker device or localization wire 20 and a probe 30 for detecting atleast a portion of the localization wire 20 using electromagneticpulses, waves, or other signals, such as radar. The localization wire 20may include an elongated member or shaft 22 including a proximal end 22a, a distal end 22 b, and a target 26 on the distal end 22 b.Optionally, the system 10 may include one or more additionallocalization wires and/or targets (not shown) in addition tolocalization wire 20.

The shaft 22 may be formed from a relatively rigid material, e.g., asolid rod or hollow tubular body, having sufficient column strength tofacilitate percutaneous introduction of the localization wire 20 throughtissue. The shaft 22 may have a length sufficient to extend from alocation outside a patient's body through tissue to a target tissueregion, e.g., between about half and ten centimeters (0.5-10 cm).Optionally, the shaft 22 may be malleable or otherwise plasticallydeformable, e.g., such that the shaft 22 may be bent or otherwise formedinto a desired shape, if desired.

The target 26 may include one or more features on the distal end 22 b ofthe shaft 22 to facilitate localization of the distal end 22 b using theprobe 30. In the exemplary embodiment shown, the target 26 may be abulbous structure, e.g., a sphere having a larger diameter than thedistal end 22 b of the shaft 22, e.g., between about half and fivemillimeters (0.5-5 mm). Optionally, the target 26 may include one ormore features to enhance electromagnetic signal reception andreflection. For example, the target 26 may be formed from one or morematerials and/or may have a surface finish that enhances detection byradar, e.g., similar to the markers described elsewhere herein. Inalternative embodiments, other shapes and/or geometries may be provided,e.g., cubes, triangles, helixes, and the like, including one or morecorners and/or edges that may enhance radar reflection and/or detection,similar to other embodiments herein.

In addition or alternatively, the target 26 may have a size and/or shapeapproximating the size and/or shape of the lesion 42, e.g., tofacilitate identifying a desired margin around the lesion 42. Forexample, the size and/or shape of the lesion 42 may be determined inadvance, and a target 26 may be selected from a set of different sizeand/or shape targets and secured to the shaft 22 (or each target may beprovided on its own shaft). In addition or alternatively, if multiplelocalization wires and/or targets are provided, each target may have adifferent shape and/or features, e.g., to facilitate distinguishing thetargets from one another using the probe 30.

In one embodiment, the shaft 22 and target 26 may be integrally formedfrom the same material. Alternatively, the target 26 may be formed fromdifferent material(s) than the shaft 22, and the target 26 may besecured to the distal end 22 b, e.g., by bonding with adhesive, welding,soldering, interference fit, threads or other cooperating connectors,and the like. Thus, in this alternative, the target 26 may be formedfrom material that enhances detection by radar relative to the shaft 22.

Optionally, if multiple targets are to be implanted, each target mayhave a surface, shape, and/or additional material feature that maydistinguish a particular target relative to one or more others. Forexample, each target may absorb or reflect a particular electromagneticsignal that is specific to that target and can be used to uniquelyidentify it.

In another option, the localization wire 20 may include one or moreanchoring elements 24 on the distal end 22 b, e.g., adjacent the target26, although the target 26 itself may stabilize the localization wire 20sufficiently that anchoring elements 24 may be unnecessary.

As shown, the anchoring elements 24 include a plurality of barbs 24 (twoshown) that extend transversely from the shaft 22, e.g., angledproximally away from the target 26. Thus, the barbs 24 may be configuredfor anchoring the localization wire 20 in position after thelocalization wire 20 is inserted into tissue, e.g., allowing thelocalization wire 20 to be advanced distally through tissue whilepreventing subsequent proximal withdrawal. For example, the barbs 24 maybe sufficiently flexible such that the barbs 24 may be compressedagainst or otherwise adjacent the shaft 22, e.g., to minimize a profileof the localization wire 20 to facilitate advancement, yet resilientlybiased to return outwardly to a transverse orientation, as shown.

The probe 30 may be a portable device having electromagnetic signalemitting and receiving capabilities, e.g., a micro-power impulse radar(MIR) probe. For example, as shown in FIG. 1, the probe 30 may be ahandheld device including a first end 30 a intended to be placed againstor adjacent tissue, e.g., a patient's skin or underlying tissue, and asecond opposite end 30 b, e.g., which may be held by a user. Withadditional reference to FIG. 10, the probe 30 generally includes one ormore antennas, e.g., a transmit antenna 32 and a receive antenna 34, oneor more processors or controllers 36, and a display 38.

Turning to FIG. 10, the processor 36 may include one or morecontrollers, circuits, signal generators, gates, and the like (notshown) needed to generate signals for transmission by the transmitantenna 32 and/or to process signals received from the receive antenna34. The components of the processor 36 may include discrete components,solid state devices, programmable devices, software components, and thelike, as desired. For example, as shown, the probe 30 may include animpulse generator 36 b, e.g., a pulse generator and/or pseudo noisegenerator (not shown), coupled to the transmit antenna 32 to generatetransmit signals, and an impulse receiver 36 c for receiving signalsdetected by the receive antenna 34. The processor 36 may include a microcontroller 36 a and a range gate control 36 d that alternately activatethe impulse generator 36 b and impulse receiver 36 c to transmitelectromagnetic pulses, waves, or other signals via the antenna 32, andthen receive any reflected electromagnetic signals via antenna 34.Exemplary signals that may be used include microwave, radio waves, suchas micro-impulse radar signals, e.g., in the Ultra Low bandwidth region.

In exemplary embodiments, each of the antennas 32, 34 may be a UWBantenna, e.g., a horn obtrusive physical profile, a dipole and patch, ora co-planar antenna, such as a diamond dipole antenna, a single endedelliptical antenna (“SEA”), a patch antenna, and the like.Alternatively, the processor 36 may activate a single antenna to operatealternately as a transmit antenna and a receive antenna (not shown)instead of providing separate antennas 32, 34.

For example, each antenna 32, 34 may be a TEM horn antenna, such as thatdisclosed in “TEM Horn Antenna for Ultra-Wide Band Microwave BreastImaging,” published in Progress in Electromagnetics Research B, Vol. 13,59-74 (2009), the entire disclosure of which is expressly incorporatedby reference herein. Alternatively, each antenna 32, 34 may be a patchantenna, such as those disclosed in U.S. Publication No. 2008/0071169,published Mar. 20, 2008, and in “Wideband Microstrip Patch AntennaDesign for Breast Cancer Tumour Detection,” by Nilavalan, et al.,published in Microwaves, Antennas, & Propagation, IET, Volume 1, Issue 2(April 2007), pp. 277-281, the entire disclosures of which are expresslyincorporated by reference herein. The patch antenna may be coupled to anenclosure (not shown), e.g., filled with dielectric material, tofacilitate use with micro-impulse radar.

In another alternative embodiment, each antenna may be a waveguide horn,e.g., as shown in FIG. 10B. As shown, antenna 32′ includes a casing 32Athat is closed on a first end 32B, and open on a second end 32C, andwithin which a waveguide 32D is mounted. The walls of the casing 32A maybe lined with an absorber material 32E, e.g., a broadband siliconeabsorber material, such as Eccosorb-FGM40, sold by Emerson & CumingMicrowave Products N.V. of Westerlo, Belgium. The volume within thecasing 32A may be filled with a dielectric 32F, e.g., having a relativepermittivity of 10. In an exemplary embodiment, the antenna 32′ may be asquare waveguide horn configured to operate at ultrawide bandfrequencies 9“UWB”) between about three and ten Gigahertz (3-10 Ghz),e.g., having a width of about fifteen by fifteen millimeters (15×15 mm),and a length between the first and second ends 32B-32C of about thirtymillimeters (30 mm). The open end 32B may be oriented outwardly from aprobe within which the antenna 32′ is mounted, e.g., such that the openend 32B may contact or otherwise be coupled with tissue through whichthe antenna 32′ is intended to transmit and/or receive signals, asdescribed elsewhere herein.

The signals from the impulse receiver 36 c may be filtered or otherwiseprocessed, e.g., by a return signal de-clutter and shaper circuit 36 e,before being communicated to the micro-controller 36 a for furtherprocessing, display, storage, transmission, and the like. The circuit 36e may receive signals from the antenna 34, e.g., return echo noise andclutter, may de-clutter the signals, e.g., using LPF, and/or may includedigital adaptive filtering and/or pulse shapers, as desired. Themicro-controller 36 a may then interpret the received and/or processedsignals to identify a spatial relationship, e.g., distance, angle,orientation, and the like, of the target 26 or other structures relativeto the probe 30, as described further below. Exemplary embodiments ofprocessors and/or other components that may be included in the probe 30are disclosed in U.S. Pat. Nos. 5,573,012 and 5,766,208, issued toMcEwan, the disclosures of which are fully and expressly incorporated byreference herein.

In an alternative embodiment, the probe 30 may be configured to operateas a magneto-radar system, such as that disclosed in U.S. Pat. No.6,914,552, issued to McEwan, the entire disclosure of which is expresslyincorporated by reference herein. For example, the probe 30 may includea magnetic field excitation source, e.g., an electromagnet (not shown),coupled to a generator and/or current coil driver (not shown), which maybe provided within or external to the probe 30. For example, the probemay induce a magnetic field to a marker or other target, generating apole to pole vibration at a specific frequency that the radar unit mayidentify and/or recognize to provide a distance measurement or locationcoordinates. Such a probe may be useful when the target is implanted intissue, bone, or bodily fluid with a relatively high impedance ordielectric constant that may attenuate the radar pulse from reaching thetarget or the reflected signal from reaching the radar antenna.

Returning to FIG. 10, the probe's display 38 may be coupled to themicro-controller 36 a for displaying information to a user of the probe30, e.g., spatial or image data obtained via the antenna(s) 32, 34. Forexample, the display 38 may simply be a readout providing distance,angle, orientation, and/or other data based on predetermined criteria,e.g., based on the relative location of the target 26 to the probe 30,as described further below. FIG. 10A shows an exemplary embodiment of anoutput for display 38 that may be provided, which may include an arrayof arrows or other indicators 38 a and a distance readout 38 b. Forexample, the microcontroller 36 a may analyze the received signals todetermine in which direction relative to the probe 30 a marker (notshown) may be located and activate the appropriate arrow 38 a, anddisplay a distance (e.g., “3 cm” shown) to the marker. Thus, the usermay be able to identify in what direction and how far in that directionthe marker is located, thereby providing the user guidance towards themarker and the target tissue region within which the marker isimplanted.

In addition or alternatively, the display 38 may provide otherinformation, e.g., real-time images of the region towards which theprobe 30 is oriented, i.e., beyond the first end 30 a, operationalparameters of the probe 30, and the like. Optionally, the probe 30 mayinclude one or more other output devices in addition to or instead ofthe display 38. For example, the probe 30 may include one or morespeakers (not shown) that may provide audio output, one or more LEDs orother light sources that provide visual output, and the like e.g., toprovide information such as spatial information, operation parameters,and the like. For example, a speaker or LED may be activated when theprobe 30 reaches a predetermined threshold distance from the marker,e.g., a desired margin, or may be activated when successively closerdistances are achieved.

Optionally, the probe 30 may include other features or components, suchas one or more user interfaces, memory, transmitters, receivers,connectors, cables, power sources, and the like (not shown). Forexample, the probe 30 may include one or more batteries or otherinternal power sources for operating the components of the probe 30.Alternatively, the probe 30 may include a cable (not shown) that may becoupled to an external power source, e.g., standard AC power, foroperating the components of the probe 30.

Returning to FIG. 10, the user controls 37 may include one or more inputdevices, such as a keypad, touch screen, individual buttons, and thelike (not shown). The user controls 37 may allow the user to performsimple operations, e.g., turn the probe 30 on and off, reset the probe30, and the like, or may allow more complicated control of the probe 30.For example, the user controls 37 may allow the sensitivity or otherparameters of the probe 30 to be adjusted, may allow data to becaptured, stored, transmitted remotely, and the like.

Optionally, the probe 30 may include internal memory 36 f that mayrecord or otherwise store data obtained via the antenna(s) 32, 34 and/ormicro-controller 36 a. For example, the micro-controller 36 a mayautomatically record data during operation, or may be instructed toselectively save data to the memory 36 f. In addition or alternatively,the microcontroller 36 a may transfer data to one or more externaldevices, e.g., for storage, display, and the like. For example, theprobe 30 may include one or more cables (not shown) to allow such datatransfer and/or the probe 30 may include a transmitter and/or receiver(not shown) for wirelessly transferring data and/or receiving commands,e.g., via radio frequency, infrared, or other signals.

As shown in FIGS. 1 and 10, all of the internal components of the probe30 may be provided in a housing or casing 39 such that the probe 30 isself-contained. For example, the casing 39 may be relatively small andportable, e.g., such that the entire probe 30 may be held in a user'shand. Optionally, as shown in FIG. 1, the first end 30 a of the casing39 may be formed from like or different materials than other portions ofthe casing 39. For example, the first end 30 a may be formed frommaterials that easily accommodate passage of electromagnetic signalstherethrough, e.g., from the transmit antenna 32 and/or to the receiveantenna 34, without substantial interference. Optionally, the materialsmay be selected to reduce interference, match impedance, or otherwisefacilitate transmitting and receiving signals via the probe 30 into andout of a patient's body. In addition or alternatively, if desired, theprobe 30 may include a handle, finger grips, and/or other features (notshown) to facilitate holding or otherwise manipulating the probe 30.

Alternatively, as shown in FIG. 11, a probe instrument 130 may beprovided that includes a separate controller 139 including one or moreof the components within a casing remote from a handheld probe 131. Forexample, the handheld probe 131 may include an elongate housing 131 aincluding a tip 131 b with one or more antennas 132. The controller 139may include one or more processors for controlling the antenna(s) 132, adisplay 138, and the like, similar to the previous embodiments. Thehandheld probe 131 may be coupled to the processor(s) in the controller139 by one or more cables 133. For example, an impulse generator,impulse receiver, and/or gate control may be provided within the casingof the controller 139 or, optionally, within the housing 131 a, ifdesired. In one embodiment, the cable 133 may be removably connectableto a connector (not shown) on the controller 139 for electricallycoupling the antenna 132 of the handheld probe 131 to the electronicswithin the controller 139. Thus, the handheld probe 131 may be adisposable, single-use device while the controller 139 may be usedduring multiple procedures by connecting a new handheld probe 131 to thecontroller 139, which may remain out of the surgical field yet remainaccessible and/or visible, as desired, as explained further below.

Turning to FIGS. 2A-5, the localization system 10 of FIG. 1 may be usedduring a medical procedure, for example, in a breast biopsy orlumpectomy procedure, e.g., to facilitate localization of a lesion orother target tissue region 42 and/or to facilitate dissection and/orremoval of a specimen from a breast 41 or other body structure. Itshould be noted that, although the system 10 is described as beingparticularly useful in localization of breast lesions, the system 10 canalso be used in localization of other objects in other areas of thebody, e.g., as described elsewhere herein.

Before the procedure, a target tissue region, e.g., a tumor or otherlesion, may be identified using conventional methods. For example, asshown in FIG. 2A, a lesion 42 within a breast 41 may be identified,e.g., using mammography and/or other imaging, and a decision may be madeto remove the lesion 42. The dashed line 44 surrounding the tumor 42defines a “clear” margin, e.g., indicating the size and shape of adesired tissue specimen 46 that is to be removed during the procedure.For example, the margin 44 may be selected to ensure that the remainingtissue after removing the specimen 46 is substantially clear ofcancerous or other undesired cells. In an exemplary embodiment, thedistance between the outer boundaries of the lesion 42 and the outeredges or margin 44 of the tissue specimen 46 may be between about oneand ten millimeters (1-10 mm), e.g., at least about two millimeters (2mm) or at least about one centimeter (1 cm).

Referring to FIGS. 2A and 2B, the localization wire 20 may be introducedpercutaneously through tissue 40, e.g., from the patient's skin 48through intervening tissue until the target 26 is positioned within thelesion 42. In an exemplary embodiment, the localization wire 20 may beintroduced through a delivery sheath (not shown), which may be placedpreviously using a needle and/or dilator (also not shown), similar tothe cannula 340 described with reference to FIGS. 20-22 elsewhereherein. For example, a cannula or delivery sheath having a sharpened tipmay be penetrated through the skin 48 and intervening tissue 40 into thelesion 42, e.g., using ultrasound or x-ray imaging for guidance, andthen the localization wire 20 may be advanced through the cannula.Alternatively, a needle having a sharpened tip may be advanced throughtissue and then a delivery sheath may be advanced over the needle (notshown), e.g., along with a dilator between the needle and deliverysheath. Once the delivery sheath is positioned such that it extends fromthe skin 48 to the lesion 42, the needle and any dilator may be removed.The distal end 22 b of the localization wire 22 may then be advancedthrough the delivery sheath until the target 26 is positioned within thelesion 42, whereupon the delivery sheath may be removed. Optionally, thelocalization wire 22 may include one or more markers (not shown) on thedistal end, e.g., radiopaque or echogenic markers, on or adjacent thetarget 26, to facilitate imaging the target 26 and/or distal end 22 b ofthe localization wire 22. External imaging may then be used duringand/or after introduction of the localization wire 20 to ensure that thetarget 26 is properly positioned within the lesion 42.

If the localization wire 20 includes anchoring element(s), such as barbs24, the barbs 24 may be compressed inwardly when the localization wire20 is advanced through the delivery sheath. Once the target 26 ispositioned within the lesion 42, the delivery sheath may be withdrawn,whereupon the barbs 24 may resiliently expand outwardly into theadjacent tissue. Thus, the barbs 24 on the distal end 22 b of the shaft22 may anchor the localization wire 20 relative to the lesion 42, e.g.,such the target 26 may be substantially secured in a fixed positionwithin the lesion 42. In addition or alternatively, a bandage, tape, andthe like (not shown) may be used to secure the proximal end 22 a of thelocalization wire 22 a to the patient's skin 48, e.g., to preventmigration of the localization wire 22.

After the localization wire 20 is correctly positioned and/or secured,the first end 30 a of the probe 30 may be placed adjacent or in contactwith the patient's skin 48, e.g., generally above the lesion 42, and/orotherwise aimed generally towards the target 26, and activated, as shownin FIG. 3. The transmit antenna 32 (not shown, see FIG. 10) of the probe30 may emit electromagnetic signals 31 that travel through the tissue 40and are reflected off of the target 26. The signals 33 may be reflectedback to the receive antenna 34 (not shown, see FIG. 10) in the probe 30.The probe 30 may then determine a spatial relationship between thetarget 26 and the first end 30 a of the probe 30, e.g., a distance 52between the target 26 and the probe 30 (and the patient's skin 48 ifcontacted by the first end 30 a of the probe 30), e.g., based on thedistance traveled by the signals 31, passage of time betweentransmission of signals 31 and reception of reflected signals 33, andthe like. Optionally, the probe 30 may also determine a relative anglebetween the target 26 and the first end 30 a, e.g., to facilitatedetermining a proper direction of dissection.

In one embodiment, the micro-controller 36 a (not shown, see FIG. 10) ofthe probe 30 may filter or otherwise analyze received signals toidentify the target 26, e.g., based on recognition of the size, shape,or other aspects of the target 26. Thus, the micro-controller 36 a mayautomatically be able to identify the target 26 and distinguish it fromother structures that may be present in the patient's body.Alternatively, the micro-controller 36 a may simply identify any objectsreflecting signals back to the probe 30, which presumably would identifythe target 26. For example, the micro-controller 36 a may calculate thedistance 52 and/or an angle relative to an axis extending orthogonallyfrom the first end 30 a of the probe 30, and display this spatialinformation on the display 38. This information may facilitatelocalizing the target 26, and consequently the lesion 42, which mayprovide guidance to a surgeon dissecting tissue overlying the lesion 42,e.g., by providing a direction and depth of dissection to access thetarget tissue region including the lesion 42.

In addition or alternatively, other information may be displayed on thedisplay 38 if desired. For example, the display 38 may provide adistance 54 between the target 26 and the outer margin 44 of the targettissue specimen 46, which may facilitate defining the targeted size andshape of the tissue specimen 46 to be removed. To determine the distance54, the probe 30 may automatically subtract a predetermined distancebetween the desired margin 44 and the target 42, e.g., based on presetparameters programmed into the processor 36 of the probe 30 or based ondimensions provided to the micro-controller 36 a by the user immediatelybefore the procedure, e.g., via user controls 37 (not shown, see FIG.10).

Optionally, with continued reference to FIG. 3, the probe 30 may bepositioned at several locations against or otherwise adjacent the skin48 and spatial information obtained, if desired. Such information mayfacilitate the surgeon determining an optimal approach path fordissection, e.g., the shortest path to the lesion 42, or otherwise helporient the surgeon relative to the lesion 42 in three dimensions. Afterthe distance 52 between the patient's skin 48 and the target 26 from adesired location on the skin 48 is determined, the tissue 40 may bedissected to reach the predetermined outer edge 44 of the tissuespecimen 46, as shown in FIG. 4. For example, an incision may be made inthe patient's skin 48 at the location where the probe 30 was placed andthe intervening tissue dissected using known methods until the depthcorresponding to the margin 44 is achieved. Optionally, at any timeduring dissection, the probe 30 may be placed against or adjacent theexposed tissue and spatial information obtained to confirm the approachand/or depth of dissection.

With continued reference to FIG. 4, if desired, once the surgeonbelieves the desired margin 44 has been reached, another lengthmeasurement may be taken with the probe 30 to verify that thepredetermined distance 54 to the target 26 has been reached. Forexample, the first end 30 a of the probe 30 may be placed in contactwith the bottom surface of the dissected tissue area, signals 31 may betransmitted by the transmit antenna 32, and signals 33 may be receivedby the receive antenna 34 in order for the probe 30 to determine thedistance between the bottom surface of the dissected tissue area and thetarget 26. After verifying that the desired margin 44 of the tissuespecimen 46 has been reached, the tissue specimen 46 may be excised orotherwise removed using conventional lumpectomy procedures with thetarget 26 remaining within the removed specimen 46. If desired, thetarget 26 may be separated from the shaft 22 to facilitate removal ofthe specimen 46, e.g., by cutting the distal end 22 b of the shaft 22,by disconnecting any connectors (not shown) between the shaft 22 andtarget 26, and the like.

Turning to FIG. 5, if desired, the probe 30 may be used to analyze theexcised tissue specimen 46, e.g., to confirm that the desired margin 44has been achieved around the target 26, and consequently around thelesion 42. As shown, transmit signals 31 are transmitted by the probe 30and signals 33 are reflected off the target 26 and received by the probe30, whereupon the probe 30 may determine and display the distance 54and/or any other spatial information. In this manner, it can be verifiedthat the predetermined tissue margin has been achieved.

Turning to FIGS. 6-9, another exemplary embodiment of a system 110 forlocalizing a lesion or other tissue structure, e.g., a plurality ofnon-palpable lesions 142, is shown that includes a probe 30 and aplurality of implantable markers or targets 120. The probe 30 may be aportable device capable of transmitting electromagnetic signals andreceiving reflected signals, similar to the embodiments describedelsewhere herein.

The markers 120 may include a plurality of implantable elements sizedfor introduction through tissue into a region surrounding the lesion142. For example, the markers 120 may be formed as a plurality ofstrips, cylinders, helixes, spheres, and the like, e.g., having featuresto enhance reflection of electromagnetic signals transmitted by theprobe 30, similar to the target 26 described above with reference toFIG. 1 and/or the markers described further elsewhere herein, e.g., withreference to FIGS. 23A-28C, 34A, 34B, 41A, and 41B.

As shown in FIG. 6, the markers 120 may be elongate strips, e.g.,rectangular or other shaped markers having a length between about halfto four millimeters (0.5-4.0 mm), a width between about half and twomillimeters (0.5-2.0 mm), and a thickness between about half and threemillimeters (0.5-3.0 mm). The markers 120 may be formed from metal orother material that may enhance detection by the probe 30, e.g., havinga desired dielectric constant. In addition or alternatively, the markers120 may be formed from bioabsorbable material, e.g., such that themarkers 120 may be implanted within tissue and then dissolved orotherwise absorbed by the tissue over time, e.g., over several days,weeks, or months.

Optionally, the markers 120 may be formed from radiopaque material,radioactive material, and/or echogenic material, which may facilitateimaging or otherwise monitoring the markers 120, e.g., duringintroduction, after placement during a procedure, or afterwards if themarkers 120 remain within the patient's body after the procedure. Inaddition, if desired, each marker 120 may have a surface, shape, and/oradditional material feature that may distinguish one or more of themarkers from others, as described elsewhere herein. For example, eachmarker 120 may modulate an incident signal from the probe 30 in apredetermined manner and/or absorb or reflect a particularelectromagnetic signal that is specific to that marker 120 and may beused to uniquely identify it.

In addition, as shown in FIG. 6, the system 110 may also include one ormore delivery devices 160 for introducing the markers 120 into apatient's body. For example, a delivery device 160 may be provided thatincludes a shaft 162 including a proximal end 162 a and a distal end 162b sized for introduction through tissue into a target tissue region (notshown) and carrying one or more markers 120. The delivery device 160 mayinclude a lumen 164 extending at least partially between the proximaland distal ends 162 a, 162 b of the shaft 162, and a pusher member 166slidable within the shaft 162 for selectively delivering one or moremarkers 120 successively or otherwise independently from the lumen 164.

As shown, the distal end 162 b of the shaft 162 may be beveled and/orotherwise sharpened such that the shaft 162 may be introduced directlythrough tissue. Alternatively, the delivery device 160 may be introducedthrough a cannula, sheath, or other tubular member (not shown)previously placed through tissue, e.g., as described elsewhere herein.Optionally, the distal end 162 b may include a band or other feature,e.g., formed from radiopaque, echogenic, or other material, which mayfacilitate monitoring the distal end 162 b during introduction, e.g.,using fluoroscopy, ultrasound, electromagnetic signals, and the like.

As shown, the pusher member 166 includes a piston or other element (notshown) disposed within the lumen 164 adjacent the marker(s) 120 and aplunger or other actuator 168 coupled to the piston for advancing thepiston to push the marker(s) 120 from the lumen 164. As shown, theplunger 168 may be manually advanced to deliver one or more markers 120successively from the lumen 164. Alternatively, a trigger device orother automated actuator (not shown) may be provided on the proximal end162 b of the shaft 162, which may advance the piston sufficiently witheach activation, e.g., to delivery an individual marker 120 from thedistal end 162 b.

Returning to FIGS. 6-9, an exemplary method is shown for using themarkers 120 and probe 30 to localize a lesion or other target tissueregion 142 within a breast 41 or other tissue structure. As shown inFIGS. 6 and 7, the markers 120 may be implanted within the tissue 40 todelineate a desired margin or volume 144 of a tissue specimen 146 to beexcised. For example, the shaft 162 of the delivery device 160 may beinserted percutaneously through the patient's skin 48, through anyintervening tissue 40, and the distal end 162 b positioned within oraround the lesion 142, e.g., using external imaging to guide the distalend 162 b to a desired location. Once in position, the plunger 168 maybe advanced (or the shaft 162 withdrawn relative to the plunger 168) todeliver a marker 120 into the tissue. The delivery device 160 may beadvanced further to another location and/or removed entirely from thebreast 41 and reintroduced through another location of the skin 48 intothe target tissue region, e.g., to deliver one or more additionalmarkers 120.

Alternatively, the delivery device 160 may carry only a single marker120, and multiple delivery devices (not shown) may be provided fordelivering each of the markers 120. In addition or alternatively, astereotactic device (not shown) may be used, e.g., to introduce one ormultiple delivery devices into the patient's body in a desiredthree-dimensional array or other arrangement for localizing the lesion142. In a further alternative, the markers 120 may be replaced withmultiple localization wires, similar to wire 10, one or more catheters(not shown) which may be delivered sequentially, simultaneously, and thelike. Optionally, the catheter(s), wire(s), or other devices may beexpandable, e.g., at a distal region (not shown) to facilitate dilatingand/or identifying a specimen volume or region.

In the exemplary embodiment shown in FIGS. 6 and 7, the markers 120surround a group of non-palpable lesions 142, e.g., before or during aprocedure to remove a specimen volume surrounding the lesions 142. Thedistance 156 between the outer edge 144 of the tissue specimen 146 andthe lesions 142 may be selected to ensure that the volume of tissueremoved is sufficient to ensure clear margins, similar to the methodsdescribed above.

As shown in FIG. 7, after the markers 120 have been implanted, the probe30 may be placed against or otherwise adjacent the patient's skin 48(e.g., it may be unnecessary to contact the patient's skin 48 with theprobe 30 to transmit and receive signals into and from the tissue 40),and the probe 30 may be used to determine the distance 152 (and/or otherspatial information) between the probe 30 and the markers 120, similarto the previous embodiments. In particular, the signals 31 emitted bythe probe 30 may be received at the markers 120 and reflected back to areceiver in the probe 30 as signals 33, and the probe 30 may use thesignals to determine the distance 152 between the patient's skin 48 andthe markers 120.

The tissue 40 surrounding the lesions 142 may then be dissected untilone of the markers 120 is encountered, as shown in FIG. 8. At thispoint, another measurement may be taken with the probe 30 to ensureproper dissection depth. The probe 30 may then be repositioned, as shownin phantom in FIG. 8, to locate another one of the markers 120 aroundthe periphery 144 of the tissue specimen 146. The resulting distancemeasurements may be used to determine a desired margin volume forexcision around the lesions 142. This process may be repeated as oftenas desired to facilitate measuring the desired margin based on thedistance to the markers 120 during excision of the tissue specimen 146around the lesions 142. The tissue specimen 146 may include the markers120 therein such that all of the markers 120 are removed with the tissuespecimen 146. Alternatively, the desired margin may be defined withinthe markers 120 such that the markers 120 remain within the breast afterthe tissue specimen 120 is removed. In this alternative, the markers 120may be bioabsorbable or may be inert and remain indefinitely within thepatient's breast 41.

Turning to FIGS. 11-15, another exemplary system and method are shownfor localizing one or more lesions 142 within a breast 41 and/orremoving a tissue specimen 146 (shown in FIGS. 14A-15A) including thelesion(s) 142. Similar to the previous embodiments, the system includesone or more markers 220 and a probe instrument 130, which may facilitatelocalizing the lesion(s) 142 and/or ensuring desired margins areachieved for the tissue specimen 146 removed from the breast 41. Theprobe instrument 130 includes a handheld probe 131 coupled to aprocessor 139 including one or more processors for controlling operationof the probe 131, as described above. Also as described above, thehandheld probe 131 includes an elongate housing 131 a including one ormore antennas 132 on or within a tip 131 b on one end of the probe 131that may be placed against the skin 48 or other tissue and/or otherwiseoriented generally towards the marker 220 and/or lesion(s) 142.

The processor 139 may include one or more processors for controlling theantenna(s) 132, a display 138, and the like, similar to the previousembodiments. The handheld probe 131 may be coupled to the processor 139by one or more cables 133. For example, an impulse generator, impulsereceiver, and/or gate control may be provided within the processor 139,which may be controlled to emit and receive signals via the antenna(s)132.

Optionally, as shown in FIGS. 14 and 14A, the handheld probe 131 mayinclude a dissecting feature 133, e.g., extending from the tip 131 b ofthe housing 131 a. In one embodiment, the dissecting feature 133 may bea relatively flat blunt dissector fixed to the tip 131 b of the probe131, e.g., having a length of about ten to fifty millimeters (10-50 mm)and/or a width of about one to ten millimeters (1-10 mm). Alternatively,the dissecting feature 133 may be retractable, e.g., such that thedissecting feature 133 may be initially retracted within the housing 131a, but may be selectively deployed when desired to dissect layers oftissue to access tissue adjacent the marker 220. In a furtheralternative, the dissecting feature 133 may include a sharpened blade oredge, which may facilitate cutting through the patient's skin 48 and/orunderlying layers of tissue 40.

Initially, as shown in FIG. 11, during use, one or more markers 220 maybe implanted within the target tissue region, e.g., using the markersand/or methods described elsewhere herein. The probe 131 may be coupledto the processor 139, e.g., by cable 133, and the tip 131 b placedagainst the skin 48. The probe 131 may be activated, e.g., to obtain aninitial distance measurement from the tip 131 b of the probe 131 to themarker 220 using the antenna(s) 132, thereby providing an approximatedistance to the lesion(s) 142. The distance measurement may be displayedon the display 138 of the processor 139, e.g., as shown in FIG. 12,and/or otherwise provided to the user. In addition or alternatively, asdescribed above, a speaker may provide the distance measurement, e.g.,using a synthesized voice, one or more tones identifying correspondingdistances, and the like, to identify the distance. For example, theprocessor 139 may analyze the received signals to determine the actualdistance from the tip 131 b of the probe 131 to the marker 220, and mayprovide the actual measurement via the speaker. Alternatively, thespeaker may provide a tone corresponding to a predetermined threshold,e.g., a first tone for a first threshold distance, a second tone ormultiple tones for a second, closer distance, and the like, therebyindicating to the user that they are getting closer to the marker 220.

As shown in FIG. 11, with the probe 131 on a first side of the breast41, a measurement L1 is obtained, while with the probe 131′ placed on asecond opposite side of the breast 41, a measurement L2 is obtained,which is greater than L1. With this information, the physician maydecide to initiate dissection on the first side since it provides ashorter path requiring less tissue dissection than a path initiated fromthe second side, as shown in FIG. 12.

Turning to FIG. 13, the probe 131 may be used to identify a desiredmargin L3 around the marker 220 and consequently around the lesion(s)142. For example, if a desired margin L3 of one centimeter (1 cm) isdesired, the probe 131 may be display or otherwise provide the actualdistance L1 from the probe 131 to the marker, as shown on the display138, thereby indicating that the probe 131 remains outside the marginL3. Alternatively, if the processor 139 knows the desired margin L3, thedisplay 138 may provide the difference between the actual distance L1and the desired margin L3 (i.e., L1-L3), thereby informing the physicianof the depth of dissection necessary to attain the desired margin.

Optionally, as shown in FIGS. 14 and 14A, if the probe 131 includes theblunt dissector 144, the blunt dissector 144 may be deployed from thetip 131 b of the probe 131 (if not permanently deployed) and advancedthrough the tissue 40 towards the marker 220, e.g., until the desiredmargin L3 is attained. The probe 131 may then be manipulated to dissecttissue around the marker 220 using the blunt dissector 144 and/or usingone or more additional dissectors, scalpels, or other tools (not shown).

As shown in FIGS. 15 and 15A, a tissue specimen 146 has been removedfrom the breast 41 that includes the marker 220 and the lesion(s) 142therein. Optionally, the probe 131 may then be used to confirm that thedesired margin L3 was achieved around the marker 220, thereby providingconfirmation that sufficient tissue has been removed from the breast 41,similar to the previous embodiments.

Turning to FIGS. 16A and 16B, still another embodiment of a system isshown that includes one or more markers 220, a probe 231 including afinger cot 231 a carrying one or more antennas 232, and a processor 239coupled to the antenna(s) 232, e.g., by cable 233. The finger cot 231 amay be a flexible sleeve, e.g., including an open end 231 b into which afinger 90 may be inserted, a closed end 231 c, and having sufficientlength to be securely received over the finger 90. For example, thefinger cot 231 a may be formed from elastic material, such as arelatively thin layer of latex, natural or synthetic rubber, and thelike, e.g., similar to surgical or examination gloves, having sufficientflexibility to expand to accommodate receiving the finger 90 whilecompressing inwardly to prevent the finger cot from 231 a sliding offthe finger 90 during use.

The antenna(s) 232 may be provided adjacent the closed end 231 c, asshown. For example, the antenna(s) 232 may include a transmit antennaand a receive antenna (not shown), similar to the previous embodiments,provided within a casing. The casing may be attached to the finger cot231 a, e.g., adjacent the closed end 231 c, for example, by bonding withadhesive, fusing, one or more overlying bands (not shown), and the like.

The processor 239 may include one or more components for operating theantenna(s) 232 and/or processing signals received from the antenna(s)232, e.g., coupled to the antenna(s) 232 by cable 233 and includingdisplay 238, similar to the previous embodiments. In the embodimentshown, the processor 239 includes one or more clips 239 a, straps,belts, clamps, or other features (not shown) that allow the processor239 to be removably secured to the arm of a user whose finger isinserted into the finger cot 231 a. For example, the clips 239 a may becurved to extend partially around a user's forearm, and the clips 239 amay be sufficiently flexible to open them to receive an arm therein andthen resiliently close to engage at least partially around the arm.Alternatively, the processor 239 may be provided in a casing (not shown)that may be placed remotely from the patient and/or user, e.g., similarto the processor 139 described above.

With additional reference to FIGS. 17 and 18, during use, a physician orother user may insert one of their fingers 90, e.g., their index fingeror thumb, into the finger cot 231 a, and the processor 239 may beactivated to send and receive signals via the antenna(s) 232, similar tothe previous embodiments.

As shown in FIG. 17, the finger 90 inserted into the finger cot 231 amay be placed against the patient's skin 48 and distance measurementsobtained to identify the distance to the marker 220. As the tissueoverlying the marker 220 is dissected, the user may insert the finger 90into the path created, as shown in FIG. 18, thereby providing directfeedback to the user of the location of the marker 220, andconsequently, the lesion(s) 142, relative to the finger 90. Thus, thisembodiment of the probe 231 may provide tactile feedback as well asdistance measurements, which may facilitate dissection and/or removal ofa tissue specimen 146 including the marker 220 and lesion(s) 142therein. For example, as shown in FIG. 17, an initial distancemeasurement L1 may be obtained informing the user of the depth ofdissection needed, while, as shown in FIG. 18, a distance measurement L2may be obtained (corresponding to the desired margin), thereby informingthe user that sufficient dissection has been achieved and the tissuespecimen 146 may be isolated and removed, similar to the previousembodiments.

Turning to FIGS. 19-22, still another system is shown for localizingand/or accessing a target tissue region, e.g., including one or morelesions 142. Generally, the system includes a probe instrument 330,including a handheld probe 331 coupled to a processor 339, similar tothe previous embodiments. For example, the probe 331 includes one ormore antennas 332, and the processor 238 includes a display 338.

In addition, the system includes a cannula or other tubular member 340that includes a proximal end 342, distal end 344, and a lumen 346extending therebetween. The cannula 340 may be a substantially rigidtubular body having a size such that the probe 331 may be receivedwithin the lumen 346, as shown in FIG. 19. As shown, the distal end 344may be beveled, sharpened, and/or otherwise formed to facilitateadvancement directly through tissue. Alternatively, the distal end 344may be tapered and/or rounded (not shown), e.g., such that the cannula340 may be advanced over a needle (not shown) either before or after theneedle has been introduced into the tissue 40, similar to the previousembodiments.

With reference to FIG. 19, before use, the probe 330 may be insertedinto the lumen 346 of the cannula 340, e.g., such that the antenna(s)332 are disposed immediately adjacent the distal end 344 of the cannula340. Optionally, the cannula 340 and/or probe 331 may include one ormore connectors (not shown) for releasably securing the probe 331relative to the cannula 340, e.g., to maintain the antenna(s) 332adjacent the distal end 344, while allowing the probe 331 to be removedwhen desired. In addition or alternatively, the cannula 340 may includeone or more seals (not shown), e.g., within the proximal end 342 and/ordistal end 344, to provide a substantially fluid-tight seal when theprobe 331 is disposed within the lumen 346 and/or when the probe 331 isremoved. For example, a hemostatic seal (not shown) may be provided inthe proximal end 342 that may provide a seal to prevent fluid flowthrough the lumen 346, yet accommodate receiving the probe 331 or otherinstruments (not shown) therethrough.

Turning to FIG. 20, during use, with the probe 331 activated and withinthe cannula 340, the distal end 344 of the cannula 340 may be insertedthrough the patient's skin 48 and tissue 40 towards the marker 220. Asshown, the probe 331 may transmit signals 31 and the display 338 of theprocessor 339 may provide a distance measurement L1 or other indicationof the relative location of the marker 220 to the antenna(s) 332 basedon the reflected signals received by the antenna(s) 332, andconsequently, relative to the distal end 344 of the cannula 340. Thus,the depth of penetration and/or direction of advancement of the cannula340 may be adjusted based upon the information provided by the probe 331and processor 339. For example, as shown in FIG. 21, the cannula 340 maybe advanced until a desired distance L2 is achieved, thereby placing thedistal end 344 a desired distance away from the marker 220, e.g., withina target tissue region adjacent the lesion(s) 142.

Turning to FIG. 22, with the distal end 344 of the cannula 340 placed ata desired location relative to the lesion(s) 142, the probe 331 may beremoved, leaving the cannula 340 in place, as shown. The cannula 340 maythereby provide a passage for accessing the target tissue region, e.g.,to perform one or more diagnostic and/or therapeutic procedure. Forexample, a needle or other tool (not shown) may be advanced through thelumen 346 of the cannula to perform a biopsy and/or to deliver fluids orother diagnostic or therapeutic material into the target tissue region.In addition or alternatively, one or more instruments (not shown) may beintroduced through the cannula 340 for removing a tissue specimen, e.g.,including the lesion(s) 142, for delivering radiation therapy, and/orother procedures. When access is no longer needed, the cannula 340 maysimply be removed. Alternatively, if it is desired to relocate thecannula 340 during a procedure, the probe 331 may be reintroduced intothe lumen 346 and the cannula 340 relocated within the tissue with theprobe 331 providing additional guidance.

In FIGS. 11-22, markers 220 are shown, which may be implanted orotherwise placed within the tissue 40, e.g., within or otherwiseadjacent the lesion(s) 142, using methods similar to those describedabove. As shown, the markers 220 are generally elongate bodies includingrelatively narrow middle stem portions between bulbous ends. The markers220 may be formed from desired materials and/or may include surfacefeatures similar to other markers herein, which may facilitatelocalization of the markers 220 and/or distinguishing markers from oneanother.

Turning to FIGS. 23A-28C, additional embodiments of markers are shownthat may be used in any of the systems and methods described herein. Forexample, turning to FIGS. 23A-23C, a first exemplary marker 320 is shownthat includes a core wire 322 carrying a plurality of beads or segments324. The core wire 322 may be an elongate member, e.g., a solid orhollow structure having a diameter or other maximum cross-sectionbetween about half and two millimeters (0.5-2 mm) and a length betweenabout one and ten millimeters (1.0-10 mm). The core wire 322 may beformed from elastic or superelastic material and/or from shape memorymaterial, e.g., stainless steel, Nitinol, and the like, such that thecore wire 322 is biased to a predetermined shape when deployed withintissue, as explained further below. Alternatively, the core wire 322 maybe substantially rigid such that the marker 320 remains in a fixedshape, e.g., linear or curved, as described further below.

As best seen in FIGS. 24A-24C, the beads 324 may include a plurality ofindividual annular bodies, e.g., each defining a portion of a generallycylindrical or spherical shape. The beads 324 may be formed from desiredmaterials similar to the previous embodiments, e.g., metals, such asstainless steel, Nitinol, titanium, and the like, plastic materials, orcomposite materials. The beads 324 may be formed by injection molding,casting, machining, cutting, grinding base material, and the like. Inaddition, a desired finish may be applied to the beads 324, e.g., bysand blasting, etching, vapor deposition, and the like.

As best seen in FIG. 24B, each bead 324 may include a passage 326therethrough for receiving the core wire 322 (not shown, see, e.g.,FIGS. 23A-23C) therethrough. The beads 324 may include shapes and/orsurface features to allow the beads 324 to be nested at least partiallyadjacent one another when secured onto the core wire 322, yet allow themarker 320 to change shape, e.g., as the core wire 322 changes shape. Inaddition, the beads 324 include surface geometries to enhance reflectionof electromagnetic waves, e.g., radar, for example, including one ormore recesses around a periphery of the beads that include multiplesurfaces with adjacent surfaces defining abrupt angles, e.g., betweenabout forty five and one hundred thirty five degrees (45-135°), or,e.g., about ninety degrees (90°). For example, as best seen in FIG. 24C,each bead 324 may include a first convex or bulbous end 324 a and asecond concave end 324 b including flat surfaces 324 d. As shown in FIG.25B, adjacent beads 324′ may define recesses 324 c′ between the flatsurfaces 324 d′ on the concave end 324 b′ of a first bead 324 and asurface 324 e′ on the bulbous end 324 a′ of the adjacent bead 324.′ Thesurfaces 324 d′ and 324 e′ may define abrupt corners therebetween, whichmay enhance detection using radar, e.g., defining angles of about ninetydegrees (90°).

Optionally, as shown in FIGS. 25A and 25B, the beads 324′ may include adesired surface finish 324 f intended to customize reflected signalsgenerated when electromagnetic signals strike the surfaces of the beads324.′ For example, the surface finish 324 f may include a plurality ofpores or dimples formed in the beads 324′ and having a desired diameterand/or depth. As explained above, the probes and processors describedelsewhere herein may analyze such reflected signals to uniquely identifya particular marker, e.g., when multiple markers are implanted orotherwise placed within a patient's body.

Returning to FIGS. 23A-23C, during assembly, a plurality of beads 324may be placed over and secured to the core wire 322 to provide afinished marker 320. For example, the core wire 322 may be insertedsuccessively through the passages 326 in the beads 324 until beads 324extend substantially between the ends of the core wire 322. The beads324 may be secured to the core wire 322, e.g., by crimping individualbeads 324 onto the core wire 322, crimping or otherwise expanding theends of the core wire 322 after sliding on sufficient beads 324, bondingwith adhesive, fusing, and the like. Thus, the beads 324 may besubstantially permanently attached to the core wire 322 such that thebeads 324 cannot move or the beads 324 may be free floating on the corewire 322, e.g., which may facilitate bending or otherwise shaping thecore wire 322, and consequently the marker 320.

Alternatively, the marker 320 may be formed from a single piece ofmaterial, e.g., such that the shapes and surfaces defined by the beads324 shown in FIGS. 23A are formed in the workpiece. In this alternative,the core wire 322 may be eliminated, or a passage may be formed throughthe workpiece for receiving the core wire 322.

In one embodiment, the marker 320 may define a substantially fixedshape, e.g., a linear shape as shown in FIGS. 23A and 23B, or acurvilinear shape, as shown in FIGS. 23D and 26A-26C. For example, thecore wire 322 of the marker 320 may be sufficiently flexible such thatthe marker 320 may be straightened, e.g., to facilitate loading themarker 320 into a delivery device and/or otherwise delivering the marker320, yet the marker 320 may be biased to a curvilinear or othernonlinear shape.

As shown in FIG. 23D, the marker 320 may be biased to assume a waveconfiguration, e.g., a serpentine or other curved shape lying within aplane. For example, the core wire 322 may be formed from elastic orsuperelastic material that is shape set such that the core wire 322 isbiased to the wave configuration, yet may be resiliently straightened toa linear configuration. The beads 324 may be spaced apart or otherwisenested such that the beads 324 do not interfere substantially with thetransformation of the core wire 322 between the linear and waveconfigurations, e.g., to facilitate loading the marker 320 into adelivery device and/or introducing the marker 320 into a body.

Alternatively, as shown in FIGS. 34A and 34B, a marker 320′″ may beprovided that is biased to assume a tapered helical shape, e.g.,including a relatively wide intermediate region 320 a′″ between taperedend regions 320 b.′″ Another alternative embodiment of a marker 320″″ isshown in FIGS. 41A and 41B that is biased to assume a substantiallyuniform diameter helical shape. One of the advantages of markers 320,′″320″″ is that they may provide a relatively constant and/or consistentRadar Cross Section (“RCS”) regardless of the reflective angle and/orposition of the markers 320,′″ 320″″ relative to the antenna(s) of theprobe (not shown). For example, even when the markers 320,′″ 320″″ areviewed along the helix axis, e.g., as viewed in FIGS. 34B and 41B, themarkers 320,′″ 320″″ may provide a RCS substantially similar to whenviewed laterally relative to the helical axis, e.g., as viewed in FIGS.34A and 41A.

Optionally, any of the markers described herein may be provided as apassive marker, an active marker, an active reflector, or an activetransponder. For example, with reference to FIGS. 23A-23D, the marker320 may simply be a “passive reflector,” i.e., the marker 320 may simplyreflect incident waves or signals striking the marker 320. The incidentsignals may be reflected off of the various surfaces and/or edges of themarker 320, e.g., thereby providing reflected waves or signals that maybe detected by a probe, as described further elsewhere herein. Onedisadvantage of a passive marker is that the Radar Cross Section (RCS)may change based on the aspect angle of the antenna of the probe and themarker 320, which may cause changes in the strength of the returnedsignal reflected from the marker 320.

Alternatively, the marker 320 may include one or more features toprovide an “active reflector,” i.e., a marker 320 that includes one ormore electronic circuits that modulate signals striking the marker 320in a predetermined manner without adding external energy or power to thereflected signals. Such a marker may include an active reflector radioelement that includes a modulated dipole or other type of activereflector antenna, e.g., including one or more very low power diodesand/or FET transistors that require very little current to operate. Theactive reflector may provide a substantially unique radar signalsignature in an embedded tissue environment that may be detected andidentified by a probe. In addition, the active reflector may provide arelatively larger signal return to the probe, e.g., thereby maintaininga target RCS regardless of antenna aspect.

For example, the marker 320 may include one or more circuits or otherelements (not shown) coupled to or embedded in the marker 320 that maymodulate incident waves or signals from the probe. In an exemplaryembodiment, a nanoscale semiconductor chip may be carried by the marker320 that does not include its own energy source and therefore merelyprocesses and modulates the signals when they are received and reflectedoff the marker 320. Exemplary embodiments of active reflectors that maybe provided on a marker are disclosed in U.S. Pat. No. 6,492,933, theentire disclosure of which is expressly incorporated by referenceherein.

FIGS. 50A and 50B show an example of modulation of a reflected signal Brelative to an incident signal A that may be achieved using an activereflector. Incident signal A may represent waves or signals transmittedby a probe (not shown), such as any of those described elsewhere herein.As shown in FIG. 50A, the incident signal A may strike and be reflectedoff of a surface, e.g., of any of the markers described herein,resulting in a reflected signal B. With a passive reflector, the surfaceof the marker may simply reflect the incident signal A, and thereforethe reflected signal B may have similar properties, e.g., bandwidth,phase, and the like, as the incident signal A.

In contrast, with an active reflector, the marker may modulate theincident signal A in a predetermined manner, for example, to change thefrequency and/or phase of the reflected signal B. For example, as shownin FIG. 50B, the circuit on the marker may change an ultrawide broadbandradar incident signal A into a relatively narrow band reflected signalB, e.g., between about one and ten GigaHertz (1-10 GHz), that alsoincludes a predetermined phase shift. The relatively narrow bandreflected signal B may enhance the RCS of the marker and thereby enhancedetection by the probe.

In addition, as shown in FIG. 50B, the phase of the reflected signal Bhas been modulated by ninety degrees (90°) relative to the incidentsignal A. If the marker is unique in this phase shift, the phase shiftmay facilitate the probe identifying and distinguishing the marker fromother structures, e.g., other markers having a different phase shift,tissue structures, and the like. For example, if multiple markers are tobe implanted in a patient's body, each marker's circuit may beconfigured to impose a different phase shift (e.g., +90°, +180°, −90°,and the like) and/or bandwidth in the reflected signal. Thus, the probemay be able to easily identify and distinguish the markers from eachother and/or from other structures in the patient's body.

One of the advantages of active reflectors is that the circuit does notrequire its own power source. Thus, the size of the circuit may besubstantially reduced and, if desired, the marker may be implantedwithin a patient's body for an extended or even indefinite period oftime, yet the marker may respond to signals from a probe to facilitatelocating and/or identifying the marker.

In a further alternative, an “active marker” may be provided thatincludes one or more features that generate detectable energy inresponse to an excitation energy reference. Examples of such activemarkers are disclosed in U.S. Pat. No. 6,363,940, the entire disclosureof which is expressly incorporated by reference herein.

In still a further alternative, an active transponder may be provided,e.g., that retransmits or “transponds” the MIR probe's energy providingfor a uniqueness of radar signal signature in an embedded tissueenvironment. The active transponder may include one or more electroniccircuits embedded in or carried by the marker and including an internalenergy source, e.g., one or more batteries, capacitors, and the like. Inan exemplary embodiment, the active transponder may include a microwavereceiver and/or transmitter, a data processing and storage element, anda modulation system for the returned signal. The active transponder maygenerate microwave energy in response to excitation microwave energyemitted by the probe, e.g., to provide a larger signal return to theprobe than would be possible with only a passive marker. For example,the marker may generate RF energy including formatted data in responseto a unique radar signature and/or frequency from the probe. In anexemplary embodiment, the active transponder may be quadrature modulatedto emit a single side band (“SSB”) signal in either the Upper SidebandBand (“USB”) or the Lower Sideband (“LSB”) of the MIR radar. Such atransponder may provide the possibility of multi-channel operationsacross the RF spectrum.

Turning to FIGS. 29A and 29B, a delivery device 260 may be provided thatincludes a shaft 262 including a proximal end 262 a and a distal end 262b sized for introduction through tissue into a target tissue region,e.g., within breast 41, and carrying a marker 320 (or optionallymultiple markers, not shown). The delivery device 260 may include alumen 264 extending between the proximal and distal ends 262 a, 262 b ofthe shaft 262, and a pusher member 266 slidable within the shaft 262 fordelivering the marker 320 of FIGS. 23A-23D from the lumen 264. As shown,the distal end 262 b of the shaft 262 may be beveled and/or otherwisesharpened such that the shaft 262 may be introduced directly throughtissue. Alternatively, the delivery device 260 may be introduced througha cannula, sheath, or other tubular member (not shown) placed throughtissue, e.g., as described elsewhere herein. Optionally, the distal end262 b may include a band or other feature, e.g., formed from radiopaque,echogenic, or other material, which may facilitate monitoring the distalend 262 b during introduction, also as described elsewhere herein.

As shown in FIG. 29A, the pusher member 266 includes a distal end 267disposed within the lumen 264 adjacent the marker 320 and a plunger orother actuator 268 for advancing the distal end 267 to push the marker320 from the lumen 264. As shown in FIG. 29B, once the distal end 264 ofthe delivery device 260 has been advanced to a desired location withintissue 40, the shaft 262 may be retracted relative to the plunger 268 toeject the markers 320 successively from the lumen 264. Alternatively, atrigger device or other automated actuator (not shown) may be providedon the proximal end 262 b of the shaft 262to delivery the marker 320from the distal end 262 b.

Turning to FIGS. 26A-26C, an alternative embodiment of a marker 320″ isshown that is generally similar to the marker 320 shown in FIGS.23A-23D, e.g., including a core wire 322″ carrying a plurality of beads324.″ Unlike the marker 320, however, the core wire 322″ is biased to ahelical shape, e.g., such that the marker 320″ is biased to a helicalconfiguration as shown. Thus, the marker 320″ may be straightened, e.g.,to facilitate loading into a delivery device, such as the deliverydevice 260 shown in FIGS. 29A and 29B, yet may be biased to returnresiliently to the helical configuration.

In an alternative embodiment, any of the markers 320, 320,′ or 320″ maybe formed at least partially from shape memory material, e.g., such thatthe markers may be biased to assume a predetermined configuration whenheated to a target temperature. For example, with reference to themarker 320 of FIG. 24, the core wire 322 may be formed from a shapememory material, e.g., Nitinol, such that the core wire 322 is in amartensitic state at or below ambient temperature, e.g., twenty degreesCelsius (20° C.) or less, and an austenitic state at or above bodytemperature, e.g., thirty seven degrees Celsius (37° C.) or more. In themartensitic state, the core wire 322 may be relatively soft andmalleable, e.g., such that the marker 320 may be straightened and loadedinto the delivery device 260 of FIGS. 29A and 29B. The shape memory ofthe core wire 322 may be heat set or otherwise programmed into thematerial such that, when the core wire 322 is heated to the targettemperature, the core wire 322 may become biased to the wave, helical,or other nonlinear shape. Thus, even if the marker 320 is bent,straightened, or otherwise deformed from its desired deploymentconfiguration while in the martensitic state, the marker 320 mayautomatically become biased to assume the deployment configuration onceintroduced into a patient's body or otherwise heated to the targettemperature.

Turning to FIGS. 27A-27C, another exemplary embodiment of a marker 420is shown. Similar to the marker 320, the marker 420 includes a core wire422 carrying a plurality of beads or segments 424. Each of the beads 424includes a plurality of recesses 424 c, e.g., for enhancing reflectionof signals from a probe (not shown), such as those described elsewhereherein. The core wire 422 and beads 424 may be manufactured andassembled similar to the previous embodiments, e.g., such that the beads424 are free to rotate on or are fixed to the core wire 422. Therecesses 424 c may be formed entirely in each respective bead 424 or maybe defined by cooperating surfaces of adjacent beads (not shown),similar to the previous embodiments. The recesses 424 c may definesubstantially flat or curved surfaces that meet at abrupt edges definingcorners that may enhance radar detection.

Optionally, as shown in FIGS. 28A-28C, alternative embodiments ofspherical markers 520, 520,′ 520″ are shown that include recesses 524 c,524 c,′ 524 c″ having different shapes and/or configurations. Therecesses 524 c, 524 c,′ 524 c″ may generate reflected signals that aresubstantially different than one another, e.g., such that a processor ofa probe may be able to distinguish different markers based on thedifferent reflected signals, as described above.

In the embodiments shown in FIGS. 28A-28C, the markers 520, 520,′ 520″are formed from a single piece of material and do not include a corewire and multiple beads. It will be appreciated that a core wire andmultiple beads may be provided, if desired, for the markers 520, 520,′520″ and/or that the marker 420 of FIGS. 27A-27C may be formed from asingle piece of material, if desired.

Turning to FIGS. 30A-31B, another embodiment of a delivery device 360 isshown that may be used for delivering a marker 320, such as the marker320 shown in FIGS. 23A-23D, but which alternatively may be any of themarkers described elsewhere herein. Generally, the delivery device 360includes a needle or other tubular shaft 362 including a proximal end362 a and a distal end 362 b sized for introduction through tissue intoa target tissue region, e.g., within breast 41, and a lumen 364extending between the proximal and distal ends 362 a, 362 b. Thedelivery device 360 also includes a pusher member 366 slidable withinthe shaft 362 for delivering the marker 320 from the lumen 364. Asshown, the distal end 362 b of the shaft 362 may be beveled and/orotherwise sharpened such that the shaft 362 may be introduced directlythrough tissue. Alternatively, the delivery device 360 may be introducedthrough a cannula, sheath, or other tubular member (not shown) placedthrough tissue, e.g., as described elsewhere herein. Optionally, thedistal end 362 b may include a band or other feature, e.g., formed fromradiopaque, echogenic, or other material, which may facilitatemonitoring the distal end 362 b during introduction, e.g., using x-rayor ultrasound imaging, also as described elsewhere herein.

As shown in FIGS. 30B and 31B, the pusher member 366 includes a distalend 367 disposed within the lumen 364, e.g., initially adjacent themarker 320 as shown in FIG. 30B. The pusher member 366 may besubstantially stationary relative to a handle 370 of the delivery device360, while the shaft 362 may be retractable, e.g., for exposing themarker 320, as described further below. For example, as shown in FIG.30B, a proximal end 366 a of the pusher member 366 may be fixed to apusher holder 372 mounted within the handle 370.

The shaft 362 may coupled to shaft holder 374, which is slidable withinthe handle 370. For example, the shaft holder 374 may be slidableaxially from a first or distal position, shown in FIG. 30B, to a secondor proximal position, shown in FIG. 31B. Thus, with the shaft holder 374in the first position, the distal end 367 of the pusher member 366 maybe offset proximally from the distal end 362 b of the shaft 362, therebyproviding sufficient space within the shaft lumen 364 to receive themarker 320, as shown in FIG. 30B. When the shaft holder 374 is directedto the second position, the shaft 362 is retracted until the distal end362 b of the shaft 362 is disposed adjacent the distal end 367 of thepusher member 366, e.g., as shown in FIG. 31B. The distal end 367 of thepusher member 366 prevents the marker 320 from migrating proximallyduring this retraction of the shaft 362 such that the marker 320 isconsequently deployed from the lumen 364 of the shaft 362, as shown inFIGS. 33 and 33A.

The shaft holder 372 and shaft 362 may be biased to the second position,but may be selectively retained in the first position, e.g., to allow amarker 320 to be loaded into and delivered using the delivery device360. For example, as shown in FIGS. 30B and 31B, the handle 370 includesa spring or other mechanism received in a recess 378 in the housing andabutting the shaft holder 374. In the first position, the spring 376 iscompressed, as shown in FIG. 30B, while in the second position, thespring 376 is relaxed or in a lower potential energy state, as shown inFIG. 31B.

The handle 370 also includes an actuator for selectively retaining andreleasing the shaft holder 374 and shaft 362 in the first position. Forexample, as shown in FIG. 30B, with the shaft holder 374 in the firstposition, the shaft holder 374 may be rotated within the handle 370until a proximal end 374 a of the shaft holder 374 abuts or otherwiseengages a distal end 372 a of the pusher holder 372. Alternatively, thehandle 370 may include one or more other features (not shown) that mayselectively engage the shaft holder 374 in the first position. As shownin FIG. 31B, if the shaft holder 374 is rotated within the handle 370 todisengage the proximal end 374 a from the distal end 372 a of the pusherholder 372, the proximal end 372 a may be free to travel proximallywithin the handle 370. Thus, once the shaft holder 374 is rotated, thespring 376 may automatically direct the shaft holder 374 proximally,thereby deploying the marker 320. It will be appreciated that otheractuators, e.g., releasable detents or locks may be provided on thehandle 370 and/or shaft holder 374 that may interact to releasablysecure the shaft 362 in its advanced position and allow the shaft 362 toautomatically retract when the actuator is activated.

Turning to FIGS. 32 and 33, the delivery device 360 may be used todeliver a marker 320 into a breast 40 or other tissue structure, e.g.,within a target tissue region including one or more lesions 142, similarto the previous embodiments. Once the marker 320 is delivered, themarker 320 may be used to localize the target tissue region, e.g., usingany of the systems and methods described elsewhere herein.

Turning to FIG. 35, still another embodiment of a marker device 610 isshown that includes a marker 620 coupled to a tether or other elongateelement 630. The tether 630 may be a suture, e.g., formed frombioabsorbable or non-absorbable material, a wire, and the like, e.g.,formed from flexible, rigid, or malleable material, and havingsufficient length to extend out of a patient's body when the marker isintroduced into a target tissue region. The marker 620 may be similar tothe marker 320″ shown in FIGS. 34A and 34B or any of the otherembodiments described elsewhere herein, and may be releasably orsubstantially permanently attached to a distal end 634 of the tether630, e.g., similar to the localization wire described elsewhere herein.Adding an elongate tether 630 extending from a marker 620 may provide anadditional reference of the location of the marker 620 when implantedwithin tissue. For example, the tether 630 may help guide a surgeon tothe exact location of the marker 620 during lumpectomy surgery and/ormay confirm the presence of the marker 620 inside a removed tumorvolume. The tether 630 may also be used to place a tag to help identifythe orientation of the marker 620 within a target tissue region, and maybe left in place or removed, as desired.

Turning to FIGS. 36-41, a delivery device 660 and method are shown forimplanting the marker device 610 within a target tissue region, e.g.,for implanting the marker 620 within a non-palpable lesion 142 within abreast 41. Similar to previous embodiments, the delivery device 660includes a shaft 262 including a proximal end 262 a and a distal end 262b sized for introduction through tissue into a target tissue region,e.g., within breast 41, and carrying the marker device 610. The deliverydevice 660 may include a lumen 664 extending at least partially betweenthe proximal and distal ends 662 a, 662 b of the shaft 662, and a pushermember 666 slidable within the shaft 662 for delivering the marker 620from the lumen 664. As shown, the distal end 662 b of the shaft 662 maybe beveled and/or otherwise sharpened such that the shaft 662 may beintroduced directly through tissue. Alternatively, the delivery device660 may be introduced through a cannula, sheath, or other tubular member(not shown) placed through tissue, e.g., as described elsewhere herein.Optionally, the distal end 662 b may include a band or other feature,e.g., formed from radiopaque, echogenic, or other material, which mayfacilitate monitoring the distal end 662 b during introduction, also asdescribed elsewhere herein.

As shown in FIG. 36, the pusher member 666 includes a lumen 667 forslidably receiving the tether 630 therethrough. Thus, duringmanufacturing or at any time before use, the marker device 610 may beloaded in the delivery device 660 such that the marker 620 is disposedwithin the lumen 664 adjacent the distal end 662 b and the tether 630extends through the lumen 667 of the pusher member 666 and out a plunger668 coupled to the pusher member 666. If the marker is 620 is biased toa helical or other shape, the marker 620 may be straightened as it isloaded into the shaft 662, as shown in FIG. 36. The marker device 610may be implanted before a lumpectomy procedure, to replace a wirelocalization procedure, or at the time of a biopsy. Alternatively, themarker device 610 may be delivered through a core needle biopsyinstrument or a vacuum assisted core needle system (not shown).

For example, during a procedure, the distal end 662 b may be insertedthrough tissue into the target tissue region, e.g., within lesion(s)142, as shown in FIG. 36. Once the distal end 662 b of the deliverydevice 660 has been advanced to a desired location within tissue, theshaft 662 may be retracted relative to a plunger 668 coupled to thepusher member 666 to deliver the marker 620 from the lumen 664, as shownin FIG. 37. As shown, the marker 620 may automatically and/orresiliently change shape upon deployment, e.g., returning towards thetapered helical shape shown in FIG. 37. Turning to FIG. 38, the deliverydevice 660 may be withdrawn from the patient's body leaving the marker620 within the target tissue region, e.g., within lesion(s) 142. Thetether 630 may simply slide through the pusher member 666 until the endis exposed from the breast 41, e.g., as shown in FIG. 39.

Optionally, as shown in FIG. 40, the tether 630 may be separated fromthe marker 620, leaving the marker 620 in place within the lesion(s)142. For example, the tether 630 may include a weakened region (notshown) immediately adjacent the marker 620, which may be broken uponapplication of a predetermined tension. Alternatively, the tether 630may include a threaded distal end 634 or other connectors that may bereleased from the marker 620, e.g., by rotating the tether 630 tounthread the distal end 634 from the marker 620. Alternatively, thetether 630 may remain attached to the marker 620 during a subsequentlumpectomy or other procedure.

Turning to FIG. 42, another exemplary embodiment of a marker device 610′is shown that is generally similar to the marker device 610, i.e.,including a tether 630 and a marker 620.′ However, the marker 620′ maybe similar to the marker 320″″ shown in FIGS. 41A and 41B. FIGS. 43-46show an exemplary embodiment of a delivery device 620′ and method forimplanting the marker device 610,′ which are generally similar to thatshown in FIGS. 36-40.

Although the systems and methods described above relate to lesionswithin breasts, one or more markers or targets may be implanted orotherwise introduced into other regions of a patient's body forsubsequent localization using a probe, such as probe 30 described above.For example, one or more targets may be placed within or adjacent a bileduct, femoral artery or vein, fallopian tube, or other body lumen forsubsequent localization. The target(s) may be carried by a catheter,wire, or other delivery device within the lumen of the body lumen from aremote access site and secured therein, e.g., by immobilizing thecatheter or wire, or by anchoring the marker(s) to, within, or throughthe wall of the body lumen or otherwise within the body lumen.

For example, FIG. 47 shows a gastrointestinal tract 3 of a patient uponwhom one or more diagnostic and/or therapeutic procedures are to beperformed. As shown, a catheter 1 carrying a marker 2 may be introducedinto the patient's GI tract 3, e.g., via the mouth or rectum. As can beseen in FIG. 48, the catheter 1 may include a marker 2, e.g., similar tothe other markers described elsewhere herein. For example, the marker 2may include features similar to one or more of the beads 320 shown inFIGS. 23A-23C and described above. The catheter 1 and marker 2 may beadvanced to a desired location within the GI tract 3, e.g., usingfluoroscopy, ultrasound, or other external imaging.

A probe, such as any of those described elsewhere herein, may then beused to locate the marker 2, and thereby locate the location in the GItract 3. It will be appreciated that other body lumens may be localizedin a similar manner, e.g., to facilitate access to the body lumen, e.g.,in a minimally invasive manner from outside the patient's body. Forexample, as shown in FIG. 49, the marker 2 may be used to locate aparticular location in the GI tract 3, e.g., to facilitate puncturingthe wall and enter the body lumen, to clip, cut, ligate, or otherwiseclose the body lumen, and the like. FIG. 49 is a cross-sectional view ofan insufflated abdomen 4, e.g., using conventional laparoscopicprocedures. A probe 5, which may be similar to any of the probesdescribed elsewhere herein, may be inserted through an access cannula 6to scan and/or detect the location of the marker 2 on the catheter 1. Alaparoscope 7 may then be used to visualize the position of the probe 5relative to the marker 2. Once the marker 2 has been located, an accesssheath 8 may be used to gain access to the GI tract 3 at the desiredlocation, e.g., to perform one or more diagnostic and/or therapeuticprocedures. The marker 2 and catheter 1 may be removed once access isachieved or after the procedure(s) is complete, as desired.

In an exemplary embodiment, a marker may be introduced into a fallopiantube using a catheter, and then a needle or other device may beintroduced in a minimally invasive manner, e.g., punctured through thepatient's skin and tissue above the marker to access the fallopian tube,for example, to ligate, cauterize, or otherwise sever or close thefallopian tube. Alternatively, if a marker is placed within a bile duct,endoscopic access may be used under guidance of the probe 30 to accessthe bile duct, e.g., to perform a procedure within a patient'sintestine. In a further alternative, markers may be placed in branchescommunicating with a length of femoral artery, vein, or other vesselintended for harvest, and then the probe 30 may be used to localize eachof the branches external to the vessel, e.g., such that each branch maybe cut, ligated, cauterized, and/or otherwise separated, to allow thelength of vessel to be separated from the adjacent vessels andharvested.

In a further alternative, one or more markers may be implanted within atarget tissue structure for localized therapy using the systemsdescribed herein. For example, the marker(s) may carry one or moredrugs, radioactive material, or other therapeutic substances that may bereleased over an extended time within or around the target tissue regionin which they are implanted. After sufficient time, e.g., after thetherapeutic substance(s) have been substantially completely depleted orotherwise sufficiently delivered, the probe 30 may be used to localizethe marker(s) to facilitate recovering and/or removing the marker(s),e.g., in a minimally invasive manner

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the scope ofthe appended claims.

1. A system for localization of a target tissue region within apatient's body, comprising: a probe comprising one or more antennas fortransmitting electromagnetic signals into a patient's body and receivingreflected signals from the patient's body, the probe analyzing thereflected signals to identify one or more objects within the patient'sbody; and a marker sized for implantation within a patient's body, themarker comprising an active reflector to enhance identification of themarker by the probe.
 2. The system of claim 1, wherein the markercomprises an elongate tether.
 3. The system of claim 1, wherein themarker comprises a plurality of beads carried by an elongate coremember, the beads configured for enhancing reflection of signals fromthe probe to facilitate identification of the marker.
 4. The marker ofclaim 1, wherein a predetermined surface finish is provided on one ormore of the beads to modulate signals reflected from the one or morebeads to enhance identification of the marker.
 5. The system of claim 1,wherein the marker comprising an electronic circuit that modulatesincident signals from the probe striking the marker such that reflectedsignals from the marker to enhance identification by the probe.
 6. Thesystem of claim 5, wherein the electronic circuit imposes a phase shifton the reflected signals, the probe configured to identify the phaseshift to distinguish the marker from other objects in the patient'sbody.
 7. The system of claim 5, wherein the probe is configured fortransmitting ultrawide band (“UWB”) signals, and wherein the electroniccircuit modulates the UWB signals such that the reflected signals have arelatively narrow band.
 8. The system of claim 1, wherein the marker isconfigured for enhancing a radar cross section (“RCS”) of the marker toenhance identification of the marker by the probe.
 9. The system ofclaim 1, wherein the marker is biased to assume a nonlinear shape yet isresiliently flexible to allow the core member to be straightened tofacilitate introduction of the marker into a target tissue region. 10.The system of claim 1, further comprising a delivery device forintroducing the marker into a patient's body.
 11. The system of claim10, wherein the delivery device comprises one of a needle and a cannula.12. A marker for localization of a target tissue region within apatient's body, comprising: an elongate core member; and a plurality ofbeads coupled to the core member, the beads comprising a plurality ofsurfaces and edges to enhance reflection of electromagnetic signals tofacilitate identification of the marker.
 13. The marker of claim 12,further comprising an electronic circuit carried by one of the beads orthe core member, the electronic circuit configured for modulatingelectromagnetic signals striking the marker such that reflected signalsenhance identification of the marker. 14-19. (canceled)
 20. A system forlocalization of a target tissue region within a patient's body,comprising: a probe comprising one or more antennas for transmittingelectromagnetic signals into a patient's body and receiving reflectedsignals from the patient's body, the probe analyzing the reflectedsignals to identify one or more objects within the patient's body; and amarker sized for implantation within a patient's body, the markercomprising an active transponder to enhance identification of the markerby the probe. 21-28. (canceled)
 29. The system of claim 1, wherein theprobe comprises a processor, the processor configured for automaticallyidentifying the target from data obtained using the one or more antennasand for determining spatial information based on the spatialrelationship of the target relative to the probe.
 30. The system ofclaim 1, wherein the probe comprises a portable device having a firstend configured to be placed against tissue of a patient's body, therebyorienting the one or more antennas towards tissues within the patient'sbody.
 31. A system for localization of a target tissue region within apatient's body, comprising: a delivery device comprising a shaftincluding a proximal end and a distal end sized for introduction throughtissue within a patient's body into a target tissue region, the deliverydevice carrying one or more markers implantable within or around thetarget tissue region; and a probe comprising one or more antennas fortransmitting and receiving electromagnetic signals to detect the one ormore markers implanted within or around the target tissue region whenthe probe is placed adjacent the target tissue region. 32-34. (canceled)35. A method for localizing a target tissue region within a patient'sbody, comprising: introducing a target through breast tissue into thetarget tissue region; placing a probe adjacent the target tissue region,the probe transmitting electromagnetic signals towards the target tissueregion, receiving electromagnetic signals reflected from the target, anddisplaying spatial information provide a spatial relationship betweenthe target and the probe; wherein the target is configured formodulating signals from the probe that strike the target such thatsignals reflected enhance identification of the target by the probe. 36.A method for localizing a target tissue region within a patient's body,comprising: introducing a target into the target tissue region; placinga probe adjacent the target tissue region; and activating the probe,whereupon the probe transmits electromagnetic signals towards the targettissue region, receives electromagnetic signals reflected from thetarget, and displays spatial information providing a spatialrelationship between the target and the probe. 37-50. (canceled)
 51. Amethod for removing a lesion within a target tissue region of apatient's breast, comprising: introducing a target through breast tissueinto the target tissue region; placing a probe adjacent the targettissue region, the probe transmitting electromagnetic signals towardsthe target tissue region, receiving electromagnetic signals reflectedfrom the target, and displaying spatial information provide a spatialrelationship between the target and the probe; and removing a tissuespecimen from the target tissue region, the tissue specimen includingthe lesion and the target. 52-55. (canceled)